Porcine reproductive and respiratory syndrome (PRRS) was first described in North Carolina (USA) in 1987. This swine disease was defined at that moment as “Mystery Swine Disease” or MSD, and was later known as “Swine Infertility and Respiratory Syndrome”, or SIRS. It next appeared in Central Europe in 1990. At the beginning, in Europe, the disease was named “Porcine Epidemic Abortion and Respiratory Syndrome” or PEARS, and, finally, “Porcine Reproductive and Respiratory Syndrome” or PRRS which became the worldwide accepted denomination.
PRRS virus is an enveloped, single-stranded RNA virus, isolated for the first time in The Netherlands, and named as Lelystad virus. It has been classified as a member of the Arteriviridae family. Viruses of the Arteriviridae family are in the Order Nidovirales. Other viruses in the Order Nidovirales are viruses in the family Coronaviridae such as coronaviruses and toroviruses.
PRRS has been described in WO92/21375. An isolate as deposited with the Collection Nationale de Culture de Micro-organismes (CNCM) of Institut Pasteur, Paris, France, under the accession number I-1102. A North American type was also isolated (WO93/03760) and the virus was deposited with the American Type Culture Collection (ATCC) under the accession number VR-2332.
In sows, the disease PRRS is characterized by reproductive disorders and respiratory symptoms. The target cells for the PRRS viruses are the macrophage cells.
One of the problems that has hindered the obtaining of immunological products against PRRS virus is the limited availability of stable substrates for virus replication.
PRRS virus could only be amplified in porcine alveolar macrophage (PAM) cultures (Wensvoort G., et al. in The Vet. Quart. 13:121-130, 1991). The need to use disease-free pigs of a certain age for the obtaining of these macrophages implied several drawbacks. Moreover, susceptibility to viral infection was not guaranteed in the recovered PAM, because cell substrates derived from different animals are always variable. This posed a major drawback in the production of antigen batches of constant and homogenous quality, and each batch needed to be evaluated in order to determine its susceptibility.
There has been research for other cell substrates. Thus, in U.S. Pat. No. 5,476,778, 15 cell lines obtained from various species (e.g., bovine, canine, feline, human, porcine, simian) and from various tissues (e.g.: kidney, lung, testicle) were tested for the culture of PRRS virus. Only one type (MA-104 cells) of 15 cell lines permits the growth of PRRS virus.
Monkey kidney cell lines (for example VERO, MA-104, MARC-145, see respectively U.S. Pat. No. 5,476,778 and WO98/00165) are used for the culture and attenuation of PRRS virus. But PRRS virus titers on these cells are low and therefore the cost of production is high.
Although inactivated and attenuated PRRS vaccines are now commercially available, it would be of great value to have alternative cell substrates to produce PRRS virus, e.g., for the production of vaccines or immunogenic compositions. And, more generally it would be of great value to have alternative cell substrates to produce pathogens, such as viruses, for instance, RNA viruses, for example, positive-strand single stranded RNA viruses, like viruses of the Order Nidovirales, such as arteviruses or viruses in the Arteriviridae family and viruses in the family Coronaviridae, e.g., for the production of vaccines or immunogenic compositions.
Moreover, it would be advantageous to provide a new cotton rat lung cell line.